The purpose of this project is to determine which animal species is most suited to be used as a model for pulmonary emphysema and to determine why the response (degree of pulmonary emphysema) to intratracheal injections of papin varies among different animal species. In answering this question, it is postulated that enzyme inhibition by an antipapain molecule plays a key role in the varied response. Preliminary studies indicate that ssch a molecule does exist. The quantity of antipapain in the sera from 6 species (rat, cat, dog, rabbit, hamsters and man) will be measured and expressed in terms of a papain inhibitory capacity (PIC). Lung lavage and lung homogenates will be studied in a similar manner. Since antibodies (to papain) are known to inhibit papain, it will be determined whether the PIC can be elevated by inducing antibodies to papain. The antipapain molecule will be purified by sequential fractionation, and its biochemical properties studied. The ability of the purified inhibitor (and antibodies to papain) to protect animal lungs from papain-induced emphysema will be studied in vitro and in situ. Such a study could provide the following: l) information concerning the most suitable animal species to be used as a model for pulmonary emphysema, 2) a key to understanding the response of various animal species to papain, 3) a clearer understanding of the mechanism by which experimental emphysema is produced by papain, and 4) whether more than one molecular species (i.e. other than alpha antitrypsin) could be important in preventing human emphysema.